[PDF][PDF] Direct reprogramming of fibroblasts into neural stem cells by defined factors

DW Han, N Tapia, A Hermann, K Hemmer, S Höing… - Cell stem cell, 2012 - cell.com
DW Han, N Tapia, A Hermann, K Hemmer, S Höing, MJ Araúzo-Bravo, H Zaehres, G Wu…
Cell stem cell, 2012cell.com
Recent studies have shown that defined sets of transcription factors can directly reprogram
differentiated somatic cells to a different differentiated cell type without passing through a
pluripotent state, but the restricted proliferative and lineage potential of the resulting cells
limits the scope of their potential applications. Here we show that a combination of
transcription factors (Brn4/Pou3f4, Sox2, Klf4, c-Myc, plus E47/Tcf3) induces mouse
fibroblasts to directly acquire a neural stem cell identity—which we term as induced neural …
Summary
Recent studies have shown that defined sets of transcription factors can directly reprogram differentiated somatic cells to a different differentiated cell type without passing through a pluripotent state, but the restricted proliferative and lineage potential of the resulting cells limits the scope of their potential applications. Here we show that a combination of transcription factors (Brn4/Pou3f4, Sox2, Klf4, c-Myc, plus E47/Tcf3) induces mouse fibroblasts to directly acquire a neural stem cell identity—which we term as induced neural stem cells (iNSCs). Direct reprogramming of fibroblasts into iNSCs is a gradual process in which the donor transcriptional program is silenced over time. iNSCs exhibit cell morphology, gene expression, epigenetic features, differentiation potential, and self-renewing capacity, as well as in vitro and in vivo functionality similar to those of wild-type NSCs. We conclude that differentiated cells can be reprogrammed directly into specific somatic stem cell types by defined sets of specific transcription factors.
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